Affinage

SMC6

Structural maintenance of chromosomes protein 6 · UniProt Q96SB8

Round 2 corrected
Length
1091 aa
Mass
126.3 kDa
Annotated
2026-04-28
64 papers in source corpus 28 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMC6 is the structural core of the essential Smc5/6 complex, a multi-subunit SMC complex that safeguards genome integrity by promoting error-free sister-chromatid recombination, resolving aberrant recombination intermediates at repetitive loci, facilitating cohesin removal from chromosome arms, and silencing extrachromosomal DNA transcription. The Smc5/6 complex comprises Smc5 and Smc6 (heterodimerizing via their hinge domains), the kleisin Nse4, the Nse1-Nse3 heterodimer, the MMS21/NSE2 SUMO E3 ligase, and the Nse5-Nse6 loader; both SMC subunits possess independent DNA-binding domains in the hinge and ATPase-head regions, with preferential binding to ssDNA modulated by ATP (PMID:25984708, PMID:22086171, PMID:15601840). SMC5/6 is recruited to double-strand breaks and stalled replication forks via the SLF1/SLF2-RAD18 axis, where MMS21-dependent SUMOylation of substrates including TRF1/TRF2 and kinetochore proteins coordinates repair pathway choice and telomere maintenance in ALT cells (PMID:25931565, PMID:17589526, PMID:23284708). SMC5/6 also restricts transcription from extrachromosomal DNA—including hepatitis B virus cccDNA—a function antagonized by HBx-mediated CRL4-dependent proteasomal degradation of SMC5 and SMC6, and resolves transcription-replication conflicts by scaffolding the BTRR-FANCM-FANCD2 pathway (PMID:26983541, PMID:27626656, PMID:41533569).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Identification of Nse1 as the first non-SMC subunit of the Smc5/6 complex established that the complex is multisubunit and nuclear, and that its integrity is essential for DNA repair.

    Evidence Co-purification, mutant analysis, and nuclear localization in budding yeast

    PMID:11927594

    Open questions at the time
    • Other non-SMC subunits not yet identified
    • Enzymatic activities of the complex unknown
  2. 2005 High

    Definition of the full subcomplex architecture (Smc5-Smc6 hinge heterodimer, Nse1-Nse3-Nse4 kleisin arm, Nse2 on the Smc5 coiled-coil, Nse5-Nse6 at the hinge) and discovery that MMS21/NSE2 is a SUMO E3 ligase provided the first enzymatic activity for the complex and explained how it connects to DNA repair signaling.

    Evidence Complex purification and yeast two-hybrid in S. pombe; in vitro SUMO ligase assays and rescue with ligase-dead mutant in human cells

    PMID:12966087 PMID:15331764 PMID:15601840 PMID:16055714

    Open questions at the time
    • No structure of full holocomplex
    • Whether SUMO ligase activity is constitutive or regulated by DNA damage unknown
  3. 2005 High

    Demonstration that smc5/6 mutants accumulate X-shaped DNA at rDNA repeats revealed the complex's role in resolving aberrant recombination intermediates at repetitive genomic loci, explaining a key source of its mitotic lethality.

    Evidence 2D gel electrophoresis and genetic suppression by rad52Δ in budding yeast

    PMID:15793567

    Open questions at the time
    • Mechanism by which the complex prevents or removes Holliday junctions not resolved
    • Whether the phenotype extends to non-rDNA repeats untested
  4. 2006 High

    ChIP-based recruitment of Smc5/6 to DSBs in yeast and humans, combined with pathway-specific repair assays, established that the complex specifically promotes sister-chromatid recombination and recruits cohesin to break sites.

    Evidence ChIP at endonuclease-induced DSBs, HR/NHEJ reporter assays, and GCR assays in yeast and human cells

    PMID:16810316 PMID:16892052

    Open questions at the time
    • Mechanism of cohesin recruitment by Smc5/6 unknown
    • Whether Smc5/6 directly contacts the recombination machinery untested
  5. 2007 High

    The MMS21 SUMO ligase activity was shown to SUMOylate TRF1/TRF2, targeting telomeres to ALT-associated PML bodies and enabling telomere recombination, while a parallel study showed Smc5/6 relocates rDNA DSB repair outside the nucleolus via SUMO-dependent mechanisms, unifying the complex's role in spatial control of recombination.

    Evidence In vitro/in vivo SUMOylation assays, IF/FISH for APBs, telomere length analysis in ALT cells; fluorescence microscopy of rDNA repair foci in yeast

    PMID:17589526 PMID:17643116

    Open questions at the time
    • Whether spatial relocalization is the sole mechanism of recombination regulation unclear
    • SUMOylation substrates at rDNA not fully catalogued
  6. 2009 High

    Smc5/6 was linked to separase-independent cohesin removal during mitosis: smc6 mutants retain arm cohesin, and Separase overexpression rescues lethality, revealing a previously unrecognized role in chromosome arm decatenation/cohesion dynamics.

    Evidence Genetic rescue by Cut1/Separase overexpression, synthetic lethality with Top2 mutants in S. pombe

    PMID:19528228

    Open questions at the time
    • Molecular mechanism of cohesin removal (topological vs. proteolytic) unresolved
    • Not confirmed in vertebrate cells
  7. 2011 High

    Biochemical characterization of purified Smc5 and Smc6 individually demonstrated that each subunit binds ssDNA preferentially and independently, with ATP-dependent modulation, localizing DNA-binding activity to both the hinge and head domains.

    Evidence EMSA with purified recombinant Smc5 and Smc6 proteins, ATPase mutant complementation

    PMID:21293191 PMID:22086171

    Open questions at the time
    • How DNA binding by individual subunits integrates in the intact holocomplex unknown
    • Stoichiometry and topology of DNA engagement not determined
  8. 2015 High

    Identification of SLF1/SLF2-RAD18 as the vertebrate-specific recruitment pathway for Smc5/6 to DNA interstrand crosslinks solved the long-standing question of how the complex is targeted to lesions in higher eukaryotes, and domain mapping confirmed dual DNA-binding domains per SMC subunit.

    Evidence CHROMASS proteomics on ICL-containing chromatin in Xenopus extracts with co-IP validation; systematic domain EMSA

    PMID:25931565 PMID:25984708

    Open questions at the time
    • Whether SLF1/2 are required for all damage types or only ICLs not tested
    • Structural basis of SLF1/2-Smc5/6 interaction unknown
  9. 2016 High

    Discovery that HBx hijacks CRL4 to degrade SMC5/6, and that SMC5/6 depletion alone derepresses extrachromosomal DNA transcription, established the complex as an innate restriction factor for episomal viral genomes—a fundamentally new function beyond DNA repair.

    Evidence Substrate-trapping proteomics, ubiquitylation assays, extrachromosomal reporter and HBV replication assays in human hepatocytes and humanized mice

    PMID:26983541 PMID:27626656

    Open questions at the time
    • Mechanism by which Smc5/6 silences extrachromosomal transcription not defined
    • Whether silencing requires SUMO ligase activity unknown at this point
  10. 2019 High

    Brc1 and Nse5-Nse6 were shown to cooperatively recruit and activate Smc5/6 SUMO ligase activity at collapsed replication forks, linking DNA damage signaling (γ-H2A) to Smc5/6 enzymatic function at the site of damage.

    Evidence Co-IP, in vivo SUMO ligase assay, and fluorescence microscopy of repair foci in fission yeast

    PMID:30348841

    Open questions at the time
    • Vertebrate ortholog of Brc1 linking γH2AX to Smc5/6 activation not identified
    • Full repertoire of damage-induced SUMOylation substrates unknown
  11. 2026 High

    An SMC5/6→BTRR→FANCM→FANCD2 linear pathway was defined for resolving transcription-replication conflicts arising from DNA supercoiling, extending the complex's role beyond classical DSB repair to R-loop/TRC biology.

    Evidence CRISPR synthetic lethality screen with SETX-deficient cells, ChIP/proximity ligation, epistasis analysis

    PMID:41533569

    Open questions at the time
    • Whether SMC5/6 directly senses supercoiling or is recruited by a sensor unknown
    • Whether SUMO ligase activity is required for BTRR recruitment untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which SMC5/6 silences extrachromosomal DNA transcription—whether through topological entrapment, SUMO-dependent chromatin compaction, or another mechanism—and the structural basis of the intact human Smc5/6 holocomplex engaged with DNA remain unresolved.
  • No structure of DNA-bound Smc5/6 holocomplex
  • Mechanism of episomal transcriptional silencing undefined at the molecular level
  • Contribution of individual DBDs to in vivo function not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0005198 structural molecule activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005694 chromosome 5 GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-1643685 Disease 2
Partners
NSMCE1NSMCE2NSMCE3NSMCE4ARAD18SLF1SLF2SMC5
Complex memberships
Smc5/6 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Nse1 and Nse2 are non-SMC subunits of the fission yeast Smc5-6 complex, identified by mass spectrometry after purification of Smc5; both are essential proteins conserved from yeast to humans, and epistasis analysis places them in the homologous recombination repair pathway with Rhp51. Affinity purification / mass spectrometry, co-immunoprecipitation, epistasis analysis The Journal of biological chemistry High 12966087
2002 Nse1 is a novel non-SMC component of the budding yeast SMC5-SMC6 complex (2–3 MDa), is essential for cell proliferation, localizes to the nucleus, and is required for DNA repair; nse1 mutants are hypersensitive to DNA-damaging agents and show aberrant mitosis. Co-purification, genetic mutant analysis, nuclear localization by microscopy The Journal of biological chemistry High 11927594
2004 Nse3 is an essential nuclear subunit of the Smc5+6 complex in fission yeast, required for mitotic chromosome segregation, DNA damage resistance, and meiosis; epistasis with Rhp51 places it in the HR repair pathway with the complex. Biochemical purification, genetic epistasis, co-immunoprecipitation Molecular biology of the cell High 15331764
2005 The Smc5/6 complex is required for segregation of repetitive chromosome regions (rDNA, telomeres) in budding yeast; smc5 and smc6 mutants accumulate X-shaped DNA (Holliday junctions) at rDNA loci, and deletion of RAD52 partially suppresses temperature sensitivity, pointing to a role in preventing sister chromatid junctions during anaphase. Conditional mutants, 2D gel electrophoresis, genetic suppression, ChIP enrichment Nature cell biology High 15793567
2005 The Smc5-Smc6 complex architecture was defined in S. pombe: two subcomplexes (Rad18-Spr18-Nse2 and Nse1-Nse3-Rad62) constitute the core; Smc5 and Smc6 interact through their hinge domains, and temperature-sensitive mutations at a conserved glycine in the Smc6 hinge abolish hinge-region interactions with Smc5. Complex purification, mass spectrometry, yeast two-hybrid, mutant characterization Molecular and cellular biology High 15601840
2005 Human MMS21 (hMMS21/NSE2), a subunit of the human SMC5/6 complex, is a SUMO E3 ligase that stimulates sumoylation of hSMC6 and the DNA repair protein TRAX; depletion of hMMS21 sensitizes HeLa cells to DNA damage-induced apoptosis, and this hypersensitivity is rescued only by wild-type hMMS21, not its ligase-inactive mutant. In vitro SUMO ligase assay, RNAi knockdown, rescue with ligase-dead mutant, comet assay Molecular and cellular biology High 16055714
2006 The Smc5-Smc6 complex is recruited de novo to DNA double-strand breaks in budding yeast and is required for repair by sister-chromatid recombination; loss of Smc5-Smc6 promotes gross chromosomal rearrangements, indicating it channels DSB repair into the error-free SCR pathway. ChIP to DSBs, genetic epistasis, chromosomal rearrangement assays Nature cell biology High 16892052
2006 Nse4 is the kleisin subunit of the Smc5-Smc6 complex that bridges the heads of Smc5 and Smc6; its C-terminal part interacts with the Smc5 head domain via a predicted winged-helix motif, and mutations in this motif abolish the Smc5 interaction. Nse3, Nse5, and Nse6 also bridge the Smc5-Smc6 heads but at different sites. Co-immunoprecipitation, yeast two-hybrid, structural prediction, mutagenesis The Journal of biological chemistry High 17005570
2006 The Nse5-Nse6 heterodimer in fission yeast constitutes a subcomplex of the Smc5/6 holocomplex; it is required for the response to stalled replication forks and UV lesion tolerance, and its UV sensitivity is suppressed by deletion of Rhp51 (Rad51), suggesting Nse5/6 suppresses aberrant HR/Holliday junction formation. Co-purification, genetic epistasis, bacterial resolvase suppression assay Molecular and cellular biology High 16478984
2006 Human SMC5/6 complex is recruited to nuclease-induced DSBs and is required for the recruitment of the SMC1/3 cohesin complex to DSBs, thereby promoting sister chromatid HR specifically without affecting NHEJ or other HR pathways. RNAi knockdown, ChIP at DSBs, HR/NHEJ reporter assays in human cells The EMBO journal High 16810316
2007 The SMC5/6 complex localizes to ALT-specific PML bodies (APBs) and is required for targeting telomeres to APBs. The MMS21 SUMO ligase subunit of SMC5/6 SUMOylates TRF1 and TRF2; inhibition of this SUMOylation prevents APB formation. Depletion of SMC5/6 inhibits telomere HR, causing telomere shortening and senescence in ALT cells. RNAi knockdown, co-immunoprecipitation, in vitro and in vivo sumoylation assays, telomere length analysis, IF/FISH Nature structural & molecular biology High 17589526
2007 The Smc5-Smc6 complex and SUMO modification of Rad52 are required for relocalization of rDNA DSB repair to an extranucleolar site; loss of Smc5-Smc6 or of Rad52 SUMO modification causes Rad52 focus formation within the nucleolus, rDNA hyperrecombination, and excision of extrachromosomal rDNA circles. Fluorescence microscopy of repair foci, SUMO modification assays, 2D gel analysis of rDNA Nature cell biology High 17643116
2008 The Nse1 RING-like domain of the Smc5-Smc6 complex is not essential for viability but is required for DNA repair functions; it acts as a protein-protein interaction domain required for Nse1-Nse3-Nse4 trimer formation in vitro and for damage-induced recruitment of Nse4 and Smc5 to subnuclear foci. No ubiquitin E3 ligase activity was detected for Nse1 in vitro. In vitro ubiquitin ligase assay, in vitro trimer reconstitution, live cell imaging of foci, mutant analysis Molecular biology of the cell High 18667531
2009 The architecture of the budding yeast Smc5/6 complex was defined: Smc5-Smc6 associate at their hinge regions; Nse1-3-4 bind to the Smc5 head and adjacent coiled-coil; Nse2 binds the middle of Smc5 coiled-coil; and the Nse5-Nse6 heterodimer uniquely contacts the hinge regions of both Smc5 and Smc6. Yeast two-hybrid, in vitro binding assays with purified recombinant proteins The Journal of biological chemistry High 19141609
2009 In fission yeast smc6 mutants, chromosome arm segregation fails after DNA damage due to aberrant persistence of cohesin that is normally removed by the Separase-independent pathway; overexpression of Separase bypasses this defect and restores viability, establishing defective cohesin removal as a major determinant of the mitotic lethality of Smc5-Smc6 mutants. Genetic rescue by Separase overexpression, synthetic lethality with topoisomerase II mutant, chromosome segregation assays Molecular and cellular biology High 19528228
2011 Smc5 binds strongly and specifically to single-stranded DNA (ssDNA) in the absence of Smc6 or other complex components; this binding is regulated by ATP, and Smc5 ATPase activity is essential for in vivo function. The minimal ssDNA length for tight Smc5 binding is ~25 nucleotides. Purified recombinant Smc5, EMSA/DNA binding assay, ATPase mutant analysis, in vivo complementation Cell cycle (Georgetown, Tex.) High 21293191
2011 Smc6 is a strong DNA-binding protein with preference for single-stranded DNA; it binds DNA independently of other Smc5-6 complex components, with binding modulated by nucleotides, and requires ~60 nucleotides for tight association. Purified recombinant Smc6, EMSA/DNA binding assay, nucleotide modulation experiments Biochemical and biophysical research communications High 22086171
2012 Nse5-Nse6 of the Smc5-Smc6 complex is required for resolution of meiotic Holliday junction intermediates; cells lacking Nse6 accumulate persistent meiotic DNA joint molecules, and this is partially rescued by expression of bacterial HJ resolvase RusA, indicating Nse5-Nse6 regulates Mus81-Eme1-dependent HJ resolution. Genetic analysis, 2D gel electrophoresis of recombination intermediates, bacterial resolvase rescue Nucleic acids research High 22855558
2012 The Smc5-Smc6 complex regulates recombination at centromeric regions during unperturbed growth; smc6 mutants accumulate recombination intermediates at centromeres (2D gels), show increased centromeric Rad52 foci, and the MMS21 SUMO ligase subunit promotes sumoylation of kinetochore proteins, affecting mitotic spindles. 2D gel electrophoresis, fluorescence microscopy of Rad52 foci, in vivo sumoylation assay, genetic suppression PloS one High 23284708
2013 SMC6 is an essential gene in mice; complete knockout causes early embryonic lethality. An S994A ATPase domain mutation (hypomorphic allele) results in reduced-size mice that are fertile, and embryonic fibroblasts are sensitive to sister chromatid exchange induction by UV and mitomycin C but not to killing by DNA damaging agents. Gene knockout/knockin in mice, phenotypic analysis, sister chromatid exchange assay, colony survival assay DNA repair High 23518413
2013 During mouse spermatogenesis, Smc6 functions as part of meiotic pericentromeric heterochromatin domains; it is dispensable for spermatogonial mitosis but Smc6-negative meiotic cells fail to complete the first meiotic division. Smc6 domains do not co-localize with γH2AX or Rad51 repair foci, suggesting a role in preventing aberrant recombination between pericentromeric regions. Immunofluorescence, co-localization analysis, conditional loss-of-function in mouse spermatogenesis Cell death & disease Medium 23907463
2015 SLF1 and SLF2 form a complex with RAD18 and define a pathway that recruits the SMC5/6 complex to DNA lesions in vertebrate cells; identification was achieved by CHROMASS proteomics on ICL-containing chromatin in Xenopus egg extracts. Chromatin mass spectrometry (CHROMASS) in Xenopus extracts, co-immunoprecipitation, functional genetics Science (New York, N.Y.) High 25931565
2015 The Smc5-Smc6 heterodimer contains two independent DNA-binding domains (DBDs) in each SMC subunit: one in the hinge region plus adjacent coiled-coil arms, and one in the ATPase head domain; heterodimerization specifically increases affinity for double-stranded DNA. Purified recombinant protein domains, EMSA, in vitro binding assays Scientific reports High 25984708
2016 HBx hijacks the cellular DDB1-CUL4 E3 ubiquitin ligase to target the SMC5/6 complex for proteasomal degradation; silencing SMC5/6 enhances extrachromosomal DNA transcription and rescues HBx-deficient HBV replication, establishing SMC5/6 as a restriction factor that directly represses extrachromosomal viral DNA transcription. Substrate-trapping proteomics, RNAi knockdown, extrachromosomal reporter assays, HBV replication assays in human hepatocytes Nature High 26983541
2016 HBx targets SMC5 and SMC6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent proteasomal degradation in human hepatocytes in vitro and in humanized mice in vivo; a dominant-negative SMC6 and SMC5/6 knockdown both rescue HBx-null HBV replication, confirming SMC5/6 restricts HBV gene expression. Substrate-trapping proteomics, ubiquitylation assay, RNAi knockdown, humanized mouse model, HBV replication assay Cell reports High 27626656
2017 The Smc5/6 complex localizes to Nuclear Domain 10 (ND10/PML bodies) in primary human hepatocytes; depletion of ND10 structural components alters nuclear distribution of Smc6 and induces HBV gene expression in the absence of HBx, indicating ND10 localization is required for Smc5/6-mediated HBV restriction. Immunofluorescence co-localization, siRNA knockdown of ND10 components, HBV gene expression assay PloS one Medium 28095508
2019 Fission yeast Brc1 promotes accumulation of the Smc5-Smc6 complex in DNA repair foci during replication stress and is required for activation of the intrinsic SUMO ligase activity of the complex by collapsed replication forks; the Nse5-Nse6 heterodimer is required for chromatin association and SUMO ligase activity of Smc5-Smc6, and Brc1 interacts with Nse5-Nse6 and γ-H2A to tether Smc5-Smc6 at replicative DNA lesions. Co-immunoprecipitation, in vivo SUMO ligase assay, fluorescence microscopy of repair foci, genetic analysis Molecular and cellular biology High 30348841
2025 Cryo-EM structure of the human HBx-CRL4-Smc5/6 complex at 3.1 Å resolution reveals that HBx adopts a Zn2+-stabilized Y-shaped architecture that simultaneously engages DDB1 and the Smc6 subunit via a composite helix-turn-helix (HTH) pocket accommodating a conserved 'Leucine Key' motif (LRCKL) on Smc6; disrupting this interface with the compound Tranilast suppresses HBV replication. Cryo-EM structure determination, biochemical reconstitution, molecular docking, antiviral assay bioRxivpreprint High
2025 SMC5/6-mediated repression of extrachromosomal circular DNA (plasmid/viral transcription) depends exclusively on the SIMC1-SLF2 subcomplex, whereas SLF1/2 is dispensable; SIMC1-SLF2 does not participate in SMC5/6 recruitment to chromosomal DNA lesions, and plasmid silencing requires a conserved SIMC1-SLF2–SMC6 interaction as well as the SUMO pathway but not PML nuclear bodies. RNAi/CRISPR knockdown, extrachromosomal reporter gene assays, co-immunoprecipitation, SUMO pathway inhibition bioRxivpreprint Medium
2026 The SMC5/6 complex is recruited to transcription-replication conflict (TRC) sites in response to DNA supercoiling buildup (in SETX-deficient cells) and facilitates recruitment of the BLM/TOP3A/RMI1/RMI2 (BTRR) complex in a TOP3A catalytic activity-dependent manner; BTRR in turn promotes FANCM accumulation and FANCD2 pathway activation, defining an SMC5/6-BTRR-FANCM-FANCD2 axis for TRC resolution. Synthetic lethality screen (CRISPR), ChIP/proximity ligation, RNAi knockdown, epistasis analysis Nucleic acids research High 41533569

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2016 Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 446 26983541
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2007 The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nature cell biology 328 17643116
2007 The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nature structural & molecular biology 312 17589526
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2016 Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Cell reports 258 27626656
2006 Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. The EMBO journal 224 16810316
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2005 Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Molecular and cellular biology 204 16055714
2015 DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science (New York, N.Y.) 193 25931565
2014 The maintenance of chromosome structure: positioning and functioning of SMC complexes. Nature reviews. Molecular cell biology 173 25145851
2006 Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nature cell biology 161 16892052
2005 SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nature cell biology 160 15793567
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2017 The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and Is Counteracted by the HBV X Protein Shortly after Infection. PloS one 125 28095508
2006 The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Molecular and cellular biology 120 16478984
2018 The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. The Journal of experimental medicine 109 30068544
2018 Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer cell 101 29478914
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2003 Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. The Journal of biological chemistry 101 12966087
2005 Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex. Molecular and cellular biology 98 15601840
2004 Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis. Molecular biology of the cell 98 15331764
2009 The unnamed complex: what do we know about Smc5-Smc6? Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 94 19308705
2006 The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits. The Journal of biological chemistry 90 17005570
2002 Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. The Journal of biological chemistry 89 11927594
2004 Coordination of DNA damage responses via the Smc5/Smc6 complex. Molecular and cellular biology 83 14701739
2009 Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. The Journal of biological chemistry 75 19141609
2004 Rad62 protein functionally and physically associates with the smc5/smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast. Molecular and cellular biology 59 15485909
2008 Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Molecular biology of the cell 54 18667531
2004 SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae. DNA repair 43 15010319
2009 Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Molecular and cellular biology 41 19528228
2012 Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6 holocomplex. Nucleic acids research 36 22855558
2011 Dynamic and selective DNA-binding activity of Smc5, a core component of the Smc5-Smc6 complex. Cell cycle (Georgetown, Tex.) 35 21293191
2013 Role for rodent Smc6 in pericentromeric heterochromatin domains during spermatogonial differentiation and meiosis. Cell death & disease 34 23907463
2012 The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth. PloS one 31 23284708
2008 Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA repair 28 18585101
2007 Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Molecular and cellular biology 26 17923688
2011 The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis. PloS one 24 21731634
2013 SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities. DNA repair 22 23518413
2019 Brc1 Promotes the Focal Accumulation and SUMO Ligase Activity of Smc5-Smc6 during Replication Stress. Molecular and cellular biology 20 30348841
2011 DNA-binding properties of Smc6, a core component of the Smc5-6 DNA repair complex. Biochemical and biophysical research communications 19 22086171
2005 Smc5-Smc6 complex preserves nucleolar integrity in S. cerevisiae. Cell cycle (Georgetown, Tex.) 19 15917663
2013 The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in Drosophila melanogaster. PloS one 17 23555814
2015 The Smc5-Smc6 heterodimer associates with DNA through several independent binding domains. Scientific reports 16 25984708
2019 Recruitment, loading, and activation of the Smc5-Smc6 SUMO ligase. Current genetics 14 30600397
2013 DNA damage checkpoint and recombinational repair differentially affect the replication stress tolerance of Smc6 mutants. Molecular biology of the cell 13 23783034
2015 Nse1 and Nse4, subunits of the Smc5-Smc6 complex, are involved in Dictyostelium development upon starvation. Development, growth & differentiation 5 26036668
2026 The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts. Nucleic acids research 0 41533569
2025 The Phenotype of Physcomitrium patens SMC6 Mutant with Interrupted Hinge Interactions. Genes 0 41010035
2025 SMC6 expression & outcome of breast cancer. The Indian journal of medical research 0 41520270